克洛素
克洛素(Klotho,或譯可羅素)是一種由人類KL基因編碼而成的酵素[5]。
該基因屬於第一型跨膜蛋白,且具有β-葡萄糖醛酸苷酶活性。慢性腎衰竭患者體內的可羅素製造會減少,這也可能是造成慢性腎衰後一連串併發症的原因(如動脈硬化、骨質疏鬆、以及皮膚鬆弛等等)。該編碼基因的突變也與老化、骨質流失有關[6][7]。過度表現可羅素的小鼠,壽命會較野生型小鼠長[8]。
功能
克洛素為一種跨膜蛋白,會調控生物體對於胰島素的敏感性,且可能也與老化有關。本蛋白最早由黑尾誠等人於1997年發現[9],該蛋白命名自希臘神話命運三女神中的克洛托(Klotho)。
克洛素具有β-葡萄糖醛酸苷酶活性,可以水解β-葡萄糖醛酸,與人類老化有關[10][11]。血漿中的循環克洛素會隨年紀逐漸減少[12]。β-克洛素會與FGF受體行程協同受體,可與FGF19、FGF20、FGF23等成纖維細胞生長因子(FGF)結合進行作用[13][14]。
克洛素缺乏的小鼠會出現類似人類早衰的症狀,並加速動脈血管硬化的進程,同時也會損傷血管新生和內皮調控血管擴張的能力。推論克洛素可能可以透過內皮源性一氧化氮釋放來保護心血管系統。
過度表現克洛素的小鼠,平均壽命會較一般小數多出19%至31%[8]。克洛速基因的某些變異還與長壽和增進認知功能相關[15]。
克洛素的作用機轉迄今未明,目前已知可以透過提升TRPV5和降低TRPC6的表達調控細胞的鈣平衡[16]。此外,克洛素也會增加內向整流離子通道ROMK的表達[16]。克洛素缺乏的小鼠會會增加維他命D的製造[17][18][19][20]。
參考文獻
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000133116 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000058488 - Ensembl, May 2017
- ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ Entrez Gene: klotho.
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- ^ Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y. alpha-Klotho as a regulator of calcium homeostasis. Science. Jun 2007, 316 (5831): 1615–8. Bibcode:2007Sci...316.1615I. PMID 17569864. doi:10.1126/science.1135901.
延伸閱讀
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